TARGETED GENE THERAPY
Subject:Crigler-Najjar Syndrome
(The following material is presented in Ascending Date Order)
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Researcher Name shown is my estimate of Principal Researcher
DB Key:1999-CN-A
Doc:JAMA
Vector:RDO RNA-DNA chimeric oligonucleotide
Experiment:Failed or Not Applicable
Of Note:Jama
1/1/1999-----Jama-----Not Applicabe
Title:New Method to Repair Faulty Genes Stirs Interest in Chimeraplasty Technique
New Method to Repair Faulty Genes Stirs Interest in Chimeraplasty Technique
Link:http://jama.ama-assn.org/issues/v281n2/ffull/jmn0113-1.html
Disease Information:http://www.crigler-najjar.com/
DB Key:1999-CN-C
Doc:Abstract
Vector:RDO RNA-DNA chimeric oligonucleotide
Experiment:Successful
Of Note:Gunn Rat
8/31/1999-----Steer CJ-----University of Minnesota
Title:Correction of the UDP-glucuronosyltransferase gene defect in the gunn rat model of crigler-najjar syndrome type I with a chimeric oligonucleotide
Link:http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10468611&dopt=Abstract
Disease Information:http://www.crigler-najjar.com/
Snippet:
Here, we show permanent correction of the UGT1A1 genetic defect in Gunn rat liver with site-specific replacement of the absent G residue at nucleotide 1206 by using an RNA/DNA oligonucleotide designed to promote endogenous repair of genomic DNA. The chimeric oligonucleotide was either complexed with polyethylenimine or encapsulated in anionic liposomes, administered i.v., and targeted to the hepatocyte via the asialoglycoprotein receptor. G insertion was determined by PCR amplification, colony lift hybridizations, restriction endonuclease digestion, and DNA sequencing, and confirmed by genomic Southern blot analysis. DNA repair was specific, efficient, stable throughout the 6-month observation period, and associated with reduction of serum bilirubin levels.
DB Key:1999-CN-D
Doc:Web Page Article
Vector:RDO RNA-DNA chimeric oligonucleotide
Experiment:Failed or Not Applicable
Of Note:Gunn Rat
9/11/1999-----Steer CJ-----University of Minnesota
Title:Gene repair in rats raises hope for genetic diseases
Link:http://www.cryonet.org/archive/12402
Disease Information:http://www.crigler-najjar.com/
Snippet:
Through the use of a novel technique termed
'chimeraplasty,' researchers have, for the first time, successfully repaired
the genetic defect associated with Crigler-Najjar syndrome, a rare but
devastating liver disease, in lab rats.
DB Key:2000-CN-R
Doc:Web Page Article
Vector:RDO RNA-DNA chimeric oligonucleotide
Experiment:Failed or Not Applicable
Of Note:None
12/30/2000-----Blaese, RM MD-----M S U D Newsletter
Title:Update on Gene Repair
Link:http://www.msud-support.org/web17_2ng.htm#gene_therapy
Disease Information:http://www.crigler-najjar.com/
Snippet:
The gene repair therapy project is continuing, albeit slowly. A young man’s death after gene therapy was widely reported in the news. This recent tragedy raised serious questions about gene therapy. The good news is that the gene repair therapy by Kimeragen does not use viruses as carriers for the gene. Even the modified viruses used in most gene therapy can cause inflammatory responses. The gene repair that is the hope for a cure in MSUD uses a molecule called a chimeraplast—a combination of DNA and RNA sequences that direct the body’s own molecular tools to repair the gene. It differs from regular gene therapy and is expected to reduce the risks.
Human trials on children with Crigler-Najjar Disease are planned for sometime next year. Extensive testing is being done to insure the safety of the therapy
DB Key:2001-CN- A
Doc:Abstract
Vector:RDO RNA-DNA chimeric oligonucleotide
Experiment:Failed or Not Applicable
Of Note:
1/1/2001-----Lai LW-----University of Arizona Health Sciences Center
Title:Therapeutic application of chimeric RNA/DNA oligonucleotide based gene therapy.
Link:http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11727546&dopt=Abstract
Disease Information:http://www.crigler-najjar.com/
Snippet:
Chimeric RNA/DNA oligonucleotides, or chimera, have emerged as a breakthrough technology for treating genetic disorders. Chimera have been shown to induce correction of point mutations in several genetic disease models without utilising the viral vectors. Recent studies of chimera-based gene therapy in genetic disease models are reviewed. Chimera were delivered intravenously, intramuscularly, intradermally, or topically with or without vehicles. Correction of the mutation at genotypic and phenotypic levels was assessed using various methods. The gene correction frequency varied, ranging from 1-40%. The resulting phenotype changes lasted longer than one year in some studies. The most dramatic phenotypic change is the reduction of serum bilirubin level by 50% in the Gunn rat, a model for Crigler-Najjar syndrome. Chimera based gene therapy has the potential to develop into powerful therapeutic modality for genetic diseases
DB Key:2001-CN-C
Doc:Abstract
Vector:RDO RNA-DNA chimeric oligonucleotide
Experiment:Failed or Not Applicable
Of Note:Mitochondria
7/1/2001-----Steer CJ-----University of Minnesota
Title:Mitochondria isolated from liver contain the essential factors required for RNA/DNA oligonucleotide-targeted gene repair
Link:http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11444824&dopt=Abstract
Disease Information:http://www.crigler-najjar.com/
Snippet:
Therefore, we determined whether mitochondria possess the enzymatic machinery for chimeric ON-mediated DNA alterations. We utilized an in vitro DNA repair assay and an Escherichia coli readout system with mutagenized plasmids carrying point mutations in antibiotic resistance genes. RNA/DNA ONs were designed to correct the defects and restore kanamycin and tetracyclin resistance. |
